JP2012012393A - Method for preparing non-alcohol bioactive essential oil mouth rinse - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for preparing a non-alcohol or alcohol-reduced mouth rinse.SOLUTION: The method relates to a liquid such as a mouth rinse for the prevention and elimination of bad breath as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. In particular, the method relates to a method for preparing a non-alcohol or alcohol-reduced mouth rinse effective for preventing the problems.

Description

  The present invention relates generally to liquids such as mouth washes for the prevention and removal of halitosis and for the reduction of oral microorganisms that are responsible for the development of plaque and caries. In particular, the present invention relates to a method for preparing a mouthwash with reduced non-alcohol or alcohol that is effective in preventing the above problems.

  Mouth rinse or mouth rinse composition is used to prevent bad breath or to remove bacteria and other oral microorganisms that cause gingival diseases such as caries, plaque, gingivitis and periodontitis as well as bad breath. Because of this, it has been used by people for many years. To this end, disinfectant mouthwashes have been devised to clean the mouth, provide a refreshing breath and disinfect these pathogenic pathogens.

  The main disinfectant mouthwash traditionally has a fairly high level of alcohol (ie ethanol), based on the total volume of mouthwash (hereinafter referred to as “% v / v”) approximately 20% to about 30% Includes in the range. Alcohols are used as both vehicles and solvents in which active ingredients and additives such as astringents, fluorides, colorants, flavor oils can be dissolved and then dispersed in solution. Alcohol also provides a preservative role for mouth washes during storage and use, and increases the sensory irritation trigger of flavor oils.

  However, the use of high levels of alcohol is sometimes found to be unacceptable to some users of mouthwash. Older people are also complaining about the problems associated with gargles from these mouthwashes, and prolonged exposure has been found to produce a gingival “burn” sensation caused by high concentrations of alcohol. Alcohol mouth washes have also been reported to cause unpleasant dry sensations.

  On the other hand, reducing the level of alcohol in these mouthwash compositions can be associated with significant disadvantages. Such disadvantages include reduced solubility of the mouthwash active and / or other mouthwash ingredients.

  For example, it has been found that reducing the alcohol concentration in a commercial mouthwash composition (ie, replacing alcohol with water) results in a cloudy or opaque composition. A clear mouthwash solution is definitely preferred by customers over a cloudy opaque or otherwise non-homogeneous cleaner solution, so a cloudy or opaque composition clearly has a disadvantage from an aesthetic point of view. To raise.

  In addition, it has been found that lower alcohol concentrations also result in a significant decrease in the ability of the composition to sterilize oral microorganisms that are responsible for halitosis, plaque and gingival disease. This loss of antibacterial activity is due not only to a decrease in alcohol as a vehicle, but also to a decrease in the bioavailability of the dissolved active substance.

  For example, thymol is a well-known antiseptic compound, also known as an essential oil, and is used in various mouthwashes or mouthwash formulations due to its antibacterial activity. In particular, thymol may be used in an oral hygiene composition such as a mouthwash sufficient to provide the desired therapeutic effect. Mouthwash solutions containing thymol are well known and have been used by many people for over 100 years. These have proven effective in killing pathogens in the oral cavity that are responsible for plaque, gingivitis and bad breath. Thymol includes the active ingredients in several disinfectant mouthwashes, along with essential oils such as methyl salicylate, menthol and eucalyptol. These oils have achieved high effectiveness despite the presence of small amounts. Without being limited to a particular theory, the effectiveness and taste of disinfectant mouthwashes is improved dispersion or dissolution of the oil and the organisms after such dispersion or dissolution of these four active ingredients. It is now believed that it may be based on anatomical availability.

  Clearly, therefore, it provides improved dispersion or solubility of essential oils that are aesthetically pleasing to the customer, while also preventing the bad breath, killing oral pathogens, reducing or eliminating plaque, and reducing the bioavailability of essential oils. There is a significant need for the development of retained, reduced alcohol and / or non-alcohol mouthwashes and methods for making these or other liquids.

  Accordingly, an aspect of the present invention is a liquid composition comprising an oil or oily component with reduced turbidity or turbidity.

  Another aspect of the present invention is an essential oil biological that is aesthetically pleasing to the customer and provides improved dispersion or solubility of the essential oil, yet prevents bad breath, kills oral pathogens, reduces or eliminates plaque. The provision of a mouth rinse composition that retains availability.

In certain embodiments, the invention is a method of preparing a liquid composition or mouth rinse,
a. ) Preparing a first premix composition comprising:
i. A first oil or oily component;
ii. Optionally a first polyol solvent;
iii. Preparing a first premix composition optionally comprising a flavoring;
b. ) Preparing a second premix composition comprising:
i. A second oil or oily component having a degree of hydrophobicity less than the hydrophobicity of the first oil or oily component; and ii. Preparing a second premix composition comprising a second polyol solvent;
c. ) Preparing a third premix composition comprising:
i. At least one surfactant, and ii. Preparing a third premix composition comprising an aqueous phase comprising water;
d. ) Adding the first premix to the third premix;
e. ) Step d. And) mixing the composition until uniform and homogeneous;
f. ) The second premix is step e. And mixing until uniform and homogeneous,
g. ) Optionally adding a sugar alcohol solvent;
h. Optionally step g. And a step of mixing until the composition becomes uniform and homogeneous.

  In some embodiments, the liquid composition or mouth rinse is a reduced alcohol or non-alcohol composition.

  In further embodiments, 0.5 (or about 0.5), optionally 1.0 (or about 1.0), optionally 2.0 (or about 2.0), or optionally 3.0 Disclosed are methods for preparing reduced alcohol or non-alcohol antibacterial mouthwash compositions that exhibit a high level of antibacterial activity, as assessed by an M-factor greater than (or about 3.0). "Is equal to the log RLU value of the biofilm treated with water used as a negative control minus the log RLU value of the biofilm treated with the mouthwash composition being tested. In addition, the oral mouthwash composition of the present invention is clear (for the human eye) and is an aesthetically attractive product.

  The liquid or mouthwash composition of the present invention may comprise any of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or restrictions described herein. Can consist of, consist of, or consist essentially of. As used herein, the term “comprising” (and grammatical variations thereof) is used to encompass “having” or “including” and includes “only”. (Consisting only of) "is not used in the exclusive sense.

  As used herein, the terms “a” and “the” are understood to include the singular and the plural.

  Unless otherwise indicated, all references cited are incorporated herein for their relevant parts, but the citation of any reference is to be construed as an admission that it is prior art relevant to the present invention. Should not. Further, all documents incorporated herein in their entirety are incorporated herein only to the extent that they do not contradict this specification.

  Reduced alcohol or non-alcohol mouthwash and mouthwash compositions described herein provide mouth odor and plaque and calculus accumulation, followed by mouth and gingival disease associated with the resulting tooth and gum disease Provide an antimicrobially effective amount of one or more antimicrobial essential oils to the microorganism.

  The phrase “antimicrobially effective amount” means the concentration or amount or level of a compound of the present invention that can achieve a particular medical purpose in a state having toxic activity against oral microorganisms.

  The phrase “orally acceptable” includes carriers applied to the oral surface or without mammals or humans without undue toxicity, incompatibility, instability, allergic reactions, etc. Meaning suitable for consumption by non-limiting organisms.

  All percentages, parts and ratios are based on the total weight of the composition of the present invention unless otherwise specified. All such weights associated with the listed ingredients are based on the level of the particular ingredient described and thus do not include carriers or by-products that may be included in commercially available materials unless otherwise specified.

The phrase “reduced alcohol” or “reduced level of alcohol” means that the liquid composition is substantially free of alcohol, which means that the liquid composition or mouthwash of the present invention is C _2- 10% v / v of the total composition of the monohydric alcohol C ₄ by volume up (or about 10% v / v), to optionally 5% v / v (or about 5% v / v), 1 optionally 0.0% v / v (or about 1.0% v / v), optionally up to 0.1% v / v (or about 0.1% v / v). Optionally, the compositions of the present invention does _not include monohydric alcohols C 2 -C _4.

  The term “sterilized water” as used herein means sterile water for washing / injection in the United States Pharmacopeia. US Pharmacopeia designation means that sterilized water for washing / injection is the subject of the current US Pharmacopoeia official monograph (date of filing of this application).

  Unless otherwise specified, “oil” or “oily component” means any hydrophobic, water-immiscible compound, essential oils (such as menthol, thymol, eucalyptol, and methyl salicylate); other flavor oils Unsaturated fatty long chain alcohols and / or aldehydes such as 1-decen-3-ol; cis-2-nonen-1-ol, trans-2-decenal and mixtures thereof; organic acids, vitamin E, vitamin E acetate , Apigenin, triclosan, and other hydrophobic compounds such as, and mixtures thereof; and mixtures of any of the hydrophobic, water-immiscible compounds disclosed above.

The term “hydrophobic”, “hydrophobic” or “hydrophobic level” of the oil or oily component of the present invention or any mixture of these oils or oily components is the octanol water partition coefficient (K _ow ). Indicated by. K _ow is the weight concentration of the oil or oily component in the octanol phase and the weight concentration of the oil or oily component in the aqueous phase in a two-phase system of octanol and water in equilibrium at a particular temperature; Ratio. The logarithm of K _ow is called log P. The experimental value used for the calculation of K _ow is usually measured at a temperature of 20 ° C. to 25 ° C.

Alternatively, the log P value is conveniently calculated by the “C LOG P” program, also available from Daylight CIS. The program also shows the log P values from the experiments when the log P experimental values are available in the Pomona 92 database. “Calculated value of log P” (C log P) is calculated according to Hansch and Leo (A. Leo, Comprehensive Medicinal Chemistry, Vol. 4, C. Hansch, P. G. Sammens, J. B. Taylor, and C.A. Ramden edit, page 295, see Pergamon Press, 1990, incorporated herein by reference). This fragment approach takes into account the number and type of atoms, the connectivity of atoms and chemical bonds based on the chemical structure of each oil or oily component. The C log P value, which is considered reliable and widely used to estimate this physicochemical property, can be used to evaluate the log P value instead of the experimental K _ow method.

  The higher the log P of the oil or oily component, the more hydrophobic the oil or oily component (or the greater the level of hydrophobicity).

  As used herein, the term “turbidity” refers to turbidity or blurring of a liquid due to individual particles (suspended solids or liquids) that are not normally visible to the naked eye. Liquids can include suspended solids or liquids of various particle sizes. Some suspended matter will be large and heavy enough that the liquid sample will settle rapidly (or separate into different layers) when the liquid sample is allowed to settle, but the sample may be stirred periodically or the particles In the colloidal state, very small particles will only slowly or not settle (or separate). These small solid or liquid particles make the liquid appear opaque.

  One of the properties of these particles is to scatter the light rays that strike them. This light scattering effect is considered to be a good measure of turbidity in water. The measurement of turbidity by this uses a device called a turbidimeter having a detector installed beside the light beam direction. If more particles are floating in the water, more light is scattered in the direction of the detector, and the value of the detected light becomes higher. A lower value of detection light means a cleaner or less turbid solution. The unit of turbidity from a calibrated turbidimeter is referred to as a turbidimetric turbidity unit (NTU). A clean formulation is defined as a formulation with an NTU of less than 12 (about 12).

First Premix Composition The liquid or mouth rinse composition of the present invention includes a first premix composition.

  In some embodiments, the first premix composition comprises a first oil or oily component and a first polyol solvent.

First oil or oily component The first premix composition of the present invention comprises a first oil or oily component, the first oil or oily component being any oil or oily component or these oils or oily component It is a mixture of In some embodiments, the first oil or oily component has a log P of 2.1 (or about 2.1), optionally 2.2 (or about 2.2) or more, or more. In certain mouthwash and other embodiments, the first oil or oily component of the present invention comprises at least one antimicrobial essential oil.

Antibacterial Essential Oils In certain embodiments, the antibacterial improved efficacy of the non-alcohol mouthwash compositions described herein is a small amount of one or more antibacterial or bioactive essential oils (ie, thymol, eucalyptol, Menthol and methyl salicylate).

_{Thymol, [(CH 3) 2 CHC} 6 H 3 (CH 3) OH, also known as isopropyl -m- cresol] is to only slightly soluble in water, soluble in alcohol, its presence This is one of the reasons why alcohol was necessary in the well-established high alcohol commercial mouthwash. Methyl salicylate (C ₆ H ₄ OHCOOCH ₃ , also known as winter green oil) further provides a scent along with its antibacterial function. Eucalyptol (C ₁₀ H ₁₈ O, also known as cineol) is a terpene ether that gives a cool, tangy taste. Eucalyptol may be used in certain formulations in place of thymol if necessary. Menthol (CH ₃ C ₆ H ₉ (C ₃ H ₇ ) OH, also known as hexahydrothymol) is also slightly soluble in alcohol and is quite volatile. Menthol provides cooling and tingling in addition to some disinfectant properties.

  In some embodiments, the essential oil is used in an amount effective to provide antimicrobial activity in the oral cavity. In a specific embodiment, the total amount of essential oil present in the disclosed composition is 0.001% (or about 0.001%) to 0.35% (or about 0.35%) w of the composition. / V, or optionally 0.16% (or about 0.16%) to 0.28% (or about 0.28%) w / v.

  In some embodiments, the composition of the present invention comprises thymol and further eucalyptol, menthol, or methyl salicylate or mixtures thereof. Optionally, the composition comprises all four of these essential oils.

  In some embodiments, thymol is 0.001% (or about 0.001%) to 0.25% (or about 0.25%) w / v of the composition, or optionally 0.04% (or about 0.04%) to 0.07% (or about 0.07%) w / v is used. In some embodiments, eucalyptol is 0.001% (or about 0.001%) to 0.11% (or about 0.11%) w / v of the composition, or optionally 0.085% (or about 0.085%) to 0.10% (or about 0.10%) w / v may be used. In some embodiments, menthol is from 0.001% (or about 0.001%) to 0.25% (or about 0.25%) w / v of the composition, or optionally 0.035% (or about 0.035%) to 0.05% (or about 0.05%) w / v is used. In some embodiments, the methyl salicylate is from 0.001% (or about 0.001%) to 0.08% (or about 0.08%) w / v of the composition, or optionally 0.04% (or An amount of about 0.04%) to 0.07% (or about 0.07%) w / v is used.

  In some embodiments, the essential oil (active ingredient) carrier is usually a water-alcohol mixture, typically water-ethanol. In the past, certain oral disinfectant mouthwash compositions required ethanol levels up to about 27% v / v. Such a high level was necessary to assist the active substance in providing a clear, aesthetically attractive liquid medium that provides the necessary antimicrobial function. Simply reducing the alcohol level without adding other formulation components results in a cloudy, less effective product.

  Without being bound by any theory, in these high alcohol level oral compositions, the alcohol acts to dissolve the antibacterial essential oil and thereby keep the essential oil bioactive. It is believed. Antibacterial essential oils disperse more easily throughout the solution, stay free and bound, and attack pathogenic pathogens throughout the oral cavity. It was believed that the reduction of alcohol levels would adversely affect this enhancement mechanism. However, according to the present invention, if the mouthwash composition comprises a solvent system and a surfactant as taught herein, the level of alcohol without sacrificing antimicrobial effectiveness or clarity. Surprisingly, it has been found that this can be reduced or eliminated.

First Polyol Solvent In certain embodiments, the first polyol solvent is added to the first premix composition. The first polyol solvent is polyhydric alkane (propylene glycol, glycerin, butylene glycol, hexylene glycol, 1,3-propanediol, etc.), polyhydric alkane ester (dipropylene glycol, ethoxydiglycol), polyalkene glycol. (Polyethylene glycol, polypropylene glycol, etc.) and polyols or polyhydric alcohols selected from the group consisting of these. In some embodiments, the polyol solvent is 0% to 20.0% (or about 20.0%) w / v of the composition, optionally 1.0% (or about 1.0%) to 15.0%. (Or about 15.0%) w / v, or optionally in an amount of 2.5% (about 2.5%) to 8.0% (or about 8.0%) w / v. .

Flavoring or Flavoring In some embodiments, to modify or enhance the taste of the liquid composition or mouthwash, and to reduce or cover strong “irritations” or “hot flashes” of ingredients such as thymol. One premix composition further comprises a flavoring or flavoring agent. Suitable flavoring agents include, but are not limited to, anise oil, anethole, benzyl alcohol, spearmint oil, citrus oil, vanillin and the like. In these embodiments, the amount of flavor oil added to the composition is 0.001% (or about 0.001%) to 1.0% (or about 1.0%) w / w of the total composition. v, or optionally 0.01% (or about 0.010%) to 0.30% (or about 0.30%) w / v.

  The particular flavor or flavor used and other taste improving ingredients will vary depending on the particular taste and feel desired. One skilled in the art can select and customize the type of ingredients to achieve the desired result.

Second Premix Composition The composition of the present invention further comprises a second premix composition.

  In certain embodiments, the second premix composition comprises a water-insoluble component and at least one polyol solvent, comprises at least one polyol solvent, or consists essentially of at least one polyol solvent. Or a solvent system.

Second oil or oily component The second premix composition of the present invention comprises a second oil or oily component, and the second oil or oily component is hydrophobic (or hydrophobic) of the second oil or oily component. Is any oil or oily component or a mixture of these oils or oily components that is lower than the hydrophobicity (or level of hydrophobicity) of the first oil or oily component. In some embodiments, the second oil or oily component has a log P of 2.1 (or about 2.1), optionally 2.0 (or about 2.0) or less, or less. In certain embodiments, the second oil or oily component of the present invention is at least one organic acid or comprises at least one organic acid. In some embodiments, the organic acid is used as part of a buffer or buffer system.

Organic acids Suitable organic acids for use in the compositions of the present invention include ascorbic acid, sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid, benzoic acid, salicylic acid, phthalic acid, phenolsulfonic acid, succinic acid and mixtures thereof The organic acid is optionally selected from the group consisting of benzoic acid, sorbic acid, succinic acid, citric acid and mixtures thereof, or optionally the organic acid is benzoic acid. In some embodiments, the organic acid buffer is in an amount of 0.001% (or about 0.001% w / v) to 1.0% w / v (or about 1.0% w / v) of the composition. Exist.

  When used as part of a buffer or buffer system, the organic acid has a pH of 3.0 (or about 3.0) to 8.0 (or about 8.0), optionally 3.5 (or about 3 .5) to 6.5 (or about 6.5), optionally incorporated in an amount to hold from 3.5 (or about 3.5) to 5.0 (or about 5.0). Without being limited by any theory, it is believed that these pH levels provide essential oils with an environment that also maximizes their antimicrobial activity and promotes stability.

  In certain embodiments, the total amount of any oil or oily component present in the disclosed compositions of the present invention is 1.35% w / v (or about 1.35% w / v of total composition). v) should not be exceeded. Optionally, the total amount of all oils or oily components is 0.04% (or about 0.04%) to 1.35% (or about 1.35%) w / v of the total composition, or optionally An amount of 0.10% (or about 0.10%) to 0.4% (or about 0.4%) w / v can be present.

Second polyol solvent A second polyol solvent is added to the second premix. In certain embodiments, the second polyol solvent may be the same as or different from the first polyol solvent, and a polyhydric alkane (such as propylene glycol, glycerin, butylene glycol, hexylene glycol, 1,3-propanediol); Polyhydric alkane esters (dipropylene glycol, ethoxydiglycol); polyalkene glycols (polyethylene glycol, polypropylene glycol, etc.) and polyols or polyhydric alcohols selected from the group consisting of these. In some embodiments, the polyol solvent is 1% (or about 1%) to 15.0% (or about 15.0%) w / v of the composition, or optionally 2.5% (or about 2.5). %) To 8.0% (or about 8.0%) w / v.

  In certain embodiments where the first polyol solvent is not added to the first premix, the second polyol solvent is 1.0% (or about 1.0%) to 30.0% (or about 30.0% of the composition). %) W / v, or optionally in an amount of 5.0% (or about 5.0%) to 15.0% (or about 15.0%) w / v.

Third Premix Composition The composition of the present invention further comprises a third premix composition. In some embodiments, the third premix composition comprises an aqueous phase surfactant.

Surfactants Suitable examples of surfactants useful in the compositions of the present invention include anionic surfactants, nonionic surfactants, amphoteric surfactants and mixtures thereof.

  Anionic surfactants useful herein include sarcosine type surfactants or sarcosinates, taurates such as sodium cocoyl methyl taurate, alkyl sulfates such as sodium trideceth sulfate or sodium lauryl sulfate, sodium lauryl sulfoacetate, lauroiylase. Examples include, but are not limited to, sodium thionate, sodium laurethcarboxylate, sodium dodecylbenzene sulfonate, and mixtures thereof. Many suitable anionic surfactants are disclosed in U.S. Pat. No. 3,959,458 to Agricola et al., Which is incorporated herein in its entirety.

  Nonionic surfactants that can be used in the compositions of the present invention include condensation of alkylene oxide groups (essentially hydrophilic) with organic hydrophobic compounds that can be essentially aliphatic or alkylaromatic. But is not limited to these. Examples of suitable nonionic surfactants include: alkyl polyglucosides; block copolymers such as ethylene oxide and propylene oxide copolymers such as poloxamers; ethoxylation marketed under the trade name CRODURET (Croda Inc., Edison, NJ) Hydrogenated castor oil; alkyl polyethylene oxides such as polysorbates; and / or aliphatic alcohol ethoxylates; polyethylene oxide condensates of alkyl phenols; products derived from the condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine; fats Long chain tertiary amine oxides; long chain tertiary phosphine oxides; long chain dialkyl sulfoxides, and mixtures thereof It is, but is not limited thereto.

  As amphoteric surfactants useful in the present invention, the aliphatic group can be linear or branched, and one of the aliphatic substituents contains from about 8 to about 18 carbon atoms, one of which is Examples include, but are not limited to, aliphatic secondary and tertiary amine derivatives containing anionic water-soluble groups such as carboxylates, sulfonates, sulfates, phosphates, or phosphonates. Examples of suitable amphoteric surfactants include alkyliminodipropionate, alkylamphoglycinate (mono or di), alkylamphopropionate (mono or di), alkylamphoacetate (mono or di), N-alkyl β-aminopropionic acid, alkylpolyaminocarboxylate, phosphorylated imidazoline, alkylbetaine, alkylamidobetaine, alkylamidopropylbetaine, alkylsultaine, alkylamidosultaines, and mixtures thereof include, but are not limited to. In some embodiments, the amphoteric surfactant is selected from the group consisting of alkylamidopropyl betaines, amphoacetates such as sodium lauroamphoacetate, and mixtures thereof. Any mixture of the above surfactants can also be used. A more detailed discussion of anionic, nonionic, and amphoteric surfactants can be found in Lennon US Pat. No. 7,087,650, Martin et al. 7,084,104, Sekiguchi et al. 190,747 and Gieske et al. 4,051,234, each of which is incorporated herein in its entirety.

In certain embodiments, the liquid or mouthwash composition comprises at least one alkyl sulfate surfactant alone or in addition to at least one of the other aforementioned surfactants. C ₈ In some embodiments, suitable alkyl sulfate surfactant C ₈ -C 18 even number alkyl sulfate _surfactant, optionally as having a chain length of C ₁₀ -C _16, sulfated -C _18, optionally the carbon chain length of even-numbered C ₁₀ -C ₁₆ sulfated include suitable basic salts, and neutralized with a mixture thereof alcohol such as sodium carbonate or sodium hydroxide However, it is not limited to these. In certain embodiments, the alkyl sulfate is selected from the group consisting of sodium lauryl sulfate, hexadecyl sulfate, and mixtures thereof. In some embodiments, a mixture of commercially available alkyl sulfates is used. A typical percentage breakdown of commercially available sodium lauryl sulfate (SLS) by alkyl chain length is as follows.

  Suitable commercially available mixtures include Stepanol WA-100 NF USP, (Stepan, Northfield, IL), Texapon K12 GPH, (Texapon, Cognis, Germany) and mixtures thereof.

  In some embodiments, the amount of alkyl sulfate surfactant added to the composition is 0.05% (or about 0.05%) to 2.0% (or about 2.0%) w / w of the composition. v, or optionally 0.1% (or about 0.1%) to 0.5% (or about 0.5%) w / v.

  The total surfactant concentration should not exceed 2% (or about 2%) or be less than 2% (or about 2%), optionally the total surfactant concentration is 1.5% (or about 1 0.5%) or less than 1.5% (or about 1.5%) and optionally the total surfactant concentration does not exceed 1.0% (or about 1.0%) Or less than 1.0% (or about 1.0%) and optionally the total surfactant concentration does not exceed 0.5% (or about 1.5%) or 0.5% (or Less than about 1.5%).

Aqueous Phase A first premix and a second premix are added to an aqueous phase containing water to make an oil-in-water or water-in-oil dispersion, microemulsion or emulsion.

  In some embodiments, the aqueous phase comprises about 60% to about 95%, or optionally about 75% to about 93% by weight of the composition.

  Alternatively, the liquid or mouthwash composition of the present invention may be formulated in the form of a dry powder, chewing gum, semi-solid, solid or concentrated liquid. In such embodiments, for example, water is added in the appropriate amount required in the case of liquid concentrates or powder formulations, or standard evaporation known in the art to produce a composition in dry powder form. Water can be removed by the method. The evaporated or lyophilized form is convenient for storage and shipping.

Sugar Alcohol Solvent In certain embodiments, a sugar alcohol is also added to the liquid or mouthwash composition of the present invention. The sugar alcohol solvent may be selected from multi-hydroxy functional compounds commonly used in oral and ingestible products. In certain embodiments, the sugar alcohol should be a non-metabolic and non-fermentable sugar alcohol. In a specific embodiment, the sugar alcohol includes sorbitol, xylitol, mannitol, maltitol, inositol, allitol, altritol, dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol, erythritol and mixtures thereof. However, it is not limited to these. Optionally, the sugar alcohol is selected from the group consisting of sorbitol and xylitol or mixtures thereof. Optionally, the sugar alcohol is sorbitol.

  In some embodiments, the total amount of sugar alcohol that can be added to effectively assist in the dispersion or dissolution of the mouthwash or other ingredients is 20% w / v (or about 20% of the total composition). w / v) should not be exceeded. Optionally, the total amount of sugar alcohol should not exceed 17% w / v (or about 17% w / v) of the total composition. Optionally, the total amount of sugar alcohol should not exceed 10% w / v (or about 10% w / v) of the total composition. Sugar alcohol is 1.0% (or about 1.0%) to 20.0% (or about 20.0%) w / v of the total composition, optionally 2.5% (or about 2.5%) ) To 17.0% (or about 17.0%) w / v, or optionally 5.0% (about 5.0%) to 15.0% (or about 15.0%) w / v Can exist.

  In some embodiments, the weight ratio of sugar alcohol to total polyol solvent component in the composition ranges from 10: 1 (or about 10: 1) to 1:10 (or about 1:10), optionally 5: 1. (Or about 5: 1) to 1: 5 (or about 1: 5), optionally 1: 1 (or about 1: 1).

  In some embodiments, the total amount of solvent includes all polyol solvents and all sugar alcohol solvents, which are added to effectively assist in the dissolution or dispersion of mouth washes or other ingredients. Although it should not exceed 47% w / v (or about 47% w / v) of the total composition. Optionally, the total amount of solvent system should not exceed 20% w / v (or about 20% w / v) of the total composition. The solvent system is 2% (or about 2%) to 47% (or about 47%) w / v of the total composition, or optionally 10% (or about 10%) to 20% (or about 20%) w / v. It can be the amount of v.

  In some embodiments, the weight ratio of total solvent (ie, polyol solvent and sugar alcohol solvent) to total surfactant in the composition is 360: 1 (or about 360: 1) to 10: 1 (or about 10). 1), optionally from 100: 1 (or about 100: 1) to 20: 1 (or about 20: 1).

Manufacturing method Each of the above-mentioned premixes is mixed until uniform and homogeneous. Each premix was mixed until uniform and homogeneous, and the first premix was immediately added to the third premix and mixed until uniform and homogeneous. Mix the mixture of the first premix and the third premix until uniform and homogeneous, and immediately add the second premix to the mixture of the first premix and the third premix and mix until uniform and homogeneous. .

  Without being limited by theory, it is believed that the first oil or oily component and the second oil or oily component compete for the surfactant and solvent in the aqueous phase of the present invention. Prior to adding the lower hydrophobicity second oil or oily component polyol solvent premix to the surfactant-containing aqueous phase, the higher hydrophobic level first oil or oily component as the polyol solvent premix. By first mixing with the aqueous phase containing the surfactant, a higher hydrophobic level of the first oil or oily component is mixed with the surfactant and / or solvent, and 12 (or about 12) turbidimetric turbidimetry. Dispersion and / or dissolution in the aqueous phase required to produce a composition having a turbidity of less than degree unit (NTU) can be achieved. Any sugar alcohol solvent can be added after the first and second oils or oily components are added to the aqueous phase to further reduce the turbidity of the liquid composition or mouth rinse.

  In some embodiments, the liquid or mouthwash of the present invention is 10 (or about 10), optionally 8 (or about 8), optionally 6 (or about 6), or optionally 4 (or about 4). Have an NTU value of less than

Optional Components Insoluble Microparticles In certain embodiments, the oral care composition of the present invention optionally includes a safe and effective amount of water-insoluble microparticles. The water-insoluble fine particles may be abrasive particles (such as a dentally acceptable abrasive) or non-abrasive fine particles.

  In certain embodiments, dentally acceptable abrasives include, but are not limited to, water-insoluble calcium salts such as calcium carbonate and various calcium phosphates, alumina, silica, synthetic resins, and mixtures thereof. Suitable dentally acceptable abrasives can be generally defined as having a radioactive dentin polishing value (RDA) of about 30 to about 250 at the concentrations used in the compositions of the present invention. In some embodiments, the abrasive is an amorphous hydrated silica abrasive, specifically, for example, under the trade names ZEODENT (JM Huber Corporation, Edison, NJ) and SYLOADENT (WR). Grace & Co., New York, NY) in the form of precipitated silica or ground silica gel. In certain embodiments, the composition according to the present invention comprises from about 1% to about 20%, or optionally from about 5% to about 10% by weight abrasive.

  Alternatively, the insoluble fine particles are non-abrasive fine particles that can be visually confirmed and are stable in the composition of the present invention.

  The non-abrasive particulates can be any size, form or color according to the desired properties of the product. Non-abrasive particulates typically have a small or substantially spherical ball or sphere shape, although plate or rod shapes are also contemplated herein. In general, the non-abrasive particulates have an average diameter of about 50 μm to about 5000 μm, optionally about 100 μm to about 3000 μm, or optionally about 300 μm to about 1000 μm. The term “stable” and / or “stability” means that abrasive or non-abrasive particulates do not decompose, aggregate or separate under normal storage conditions. In certain embodiments, the terms “stable” and / or “stability” include signs that the composition of the present invention is visible for insoluble particulate precipitation after 8 weeks at room temperature, optionally after 26 weeks, and optionally after 52 weeks. It further means whether it contains no signs or only slight visible signs (with the naked eye).

  The non-abrasive particulates herein are typically about 0.01% to about 25%, optionally about 0.01% to about 5%, or optionally about 0.05% by weight of the composition. Incorporated into the composition at a concentration of from wt% to about 3 wt%.

  The non-abrasive particulates herein typically include structural materials and / or optionally included materials.

  The structural material imparts a particular strength to the non-abrasive particulates so as to retain a clearly detectable structure in the composition of the present invention under normal storage conditions. In one embodiment, the structural material can also be broken and broken down with very little shear on the teeth, tongue, or oral mucosa during use.

  The non-abrasive particulates may be solid or liquid and may or may not be clogged as long as they are stable in the composition of the present invention. The structural material used to make the non-abrasive particulates will vary depending on the compatibility with the other components and, if present, the materials encapsulated in the non-abrasive particulates. Typical materials for the preparation of non-abrasive fine particles in this specification include crystalline cellulose, cellulose acetate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose nitrate, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate , Methylcellulose, sodium carboxymethylcellulose, gum acacia (gum arabic), agar, agarose, maltodextrin, sodium alginate, calcium alginate, dextran, starch, galactose, glucosamine, cyclodextrin, chitin, amylose, amylopectin, glycogen, laminaran, lichenan, Curdlan, inulin, levan, pectin, mannan, ki Polysaccharides and saccharide derivatives such as orchid, alginic acid, arabic acid, glucomannan, agarose, agaropectin, profilan, carrageenen, fucoidan, glycosamminglican, hyaluronic acid, chondroitin, peptidoglycan, lipopolysaccharide, guar gum, starch and starch derivatives; Oligosaccharides such as sucrose, lactose, maltose, uronic acid, muramic acid, cellobiose, isomaltose, planteose, melezitose, gentianose, maltotriose, stachyose, glucoside and polyglucoside; monosaccharides such as glucose, fructose and mannose; poly Acrylic polymers and copolymers including acrylamide, poly (alkyl cyanoacrylate), and poly (ethylene vinyl) Acetoacetate) and carboxyvinyl polymer, polyamide, poly (methyl vinyl ether-maleic anhydride), poly (adipyl-L-lysine), polycarbonate, polyterephthalamide, polyvinyl acetate phthalate, poly (terephthaloyl-L-lysine), Polyarylsulfone, poly (methyl methacrylate), allyl methacrylate, poly (ε-caprolactone), polyvinylpyrrolidone, polydimethylsiloxane, polyoxyethylene, polyester, polyglycolic acid, polylactic acid, polyglutamic acid, polylysine, polystyrene, poly (styrene) -Synthetic polymers such as acrylonitrile), polyimide, and poly (vinyl alcohol); oils, fatty acids, aliphatic alcohols, milk solids, molasses, gelatin, gluten, al Min, shellac, caseinate, beeswax, carnauba wax, whale wax, hydrogenated tallow, glycerol monopalmitate, glycerol dipalmitate, hydrogenated castor oil, glycerol monostearate, glycerol distearate, glycerol tristearate, Other substances such as 12 hydroxystearyl alcohol, proteins, and protein derivatives; and mixtures thereof. The components herein may be described in other sections as useful components of the composition. In some embodiments, the components described in this section form a non-abrasive particulate structure that does not substantially dissolve or disperse from the particulate into the composition of the invention under normal storage conditions. ing.

  In other embodiments, the structural material herein includes or is optionally a component selected from the group consisting of saccharides and derivatives thereof, saccharides and derivatives thereof, oligosaccharides, monosaccharides, and mixtures thereof. Contains ingredients with various solubility in water. In some embodiments, the structural material comprises lactose, cellulose, and hydroxypropylmethylcellulose.

  Suitable non-abrasive particulates also include organogel particles described in detail in US Pat. No. 6,797,683. Non-abrasive fine particles, which are organic gel particles, are usually made of wax (for example, beeswax, paraffin, water-insoluble wax, carbon-based wax, silicone wax, microcrystalline wax, etc.), triglyceride, acid triglyceride, polymer, fluoroalkyl (metaalkyl). ) Acrylate polymers and copolymers, acrylate polymers, ethylene / acrylate copolymers, polyethylene, polypropylene polymers and copolymers, fatty acids, fatty alcohols, fatty acid esters, fatty acid ethers, fatty acid amides, alkylene polyhydric alcohols, alkanolamine fatty acid amides, glyceryl Monostearate, (aryl-substituted) sugar, dibenzylsorbitol (or mannitol, rabitol, etc.), condensates and precondensates of lower monohydric alcohols, Alcohols, lower polyglycols, are selected from propylene / ethylene polycondensates, including structural materials. Optionally, structural materials for non-abrasive particulates that are organic gel particles include beeswax, carnauba wax, low molecular weight ethylene homopolymers (eg, Polywax 500, Polywax 1000, or Polywax available from Baker Petrolite Corp.). 2000 polyethylene material), or paraffin wax.

  The non-abrasive fine particles in the present specification may include, contain, or fill an internal packaging material. Such inclusion substances can be water-soluble or water-insoluble. Suitable encapsulants include oral care actives, vitamins, pigments, dyes, antibacterial agents, chelating agents, optical brighteners, flavoring agents, fragrances, moisturizers, minerals, and mixtures thereof herein. Mention may be made of the beneficial substances described. The encapsulating material herein is substantially retained within the non-abrasive particulates and does not substantially dissolve from the particulates into the composition of the present invention under normal storage conditions.

  Commercially available non-abrasive particulates particularly useful herein are trade names Unisphere and Unicerin, available from Induchem AG (Switzerland), and United-Guard Inc. Confetti Dental Essentials available from (New York, USA). Unisphere and Unicerin particles are made of microcrystalline cellulose, hydroxypropyl cellulose, lactose, vitamins, pigments, and proteins. In use, Unisphere and Unicerin particles can degrade with very little shear and virtually no resistance and are easily dispersed in the compositions of the present invention.

  Suitable non-abrasive particulates for incorporation into the composition are US Pat. No. 6,797,683 (organogel particles), US Pat. No. 6,045,813 (ruptureable beads), US Patent Application Publication No. 2004. / 0047822 A1 (visible capsules) and US Pat. No. 6,106,815 (encapsulated or micronized oily substances), each of which is hereby incorporated by reference in its entirety. .

  In some embodiments, the abrasive and / or non-abrasive particles have a density that is different from, or optionally substantially different from, the carrier in which the particles are incorporated.

Fluoride-releasing compound In certain embodiments, a compound that provides fluoride may be present in the mouth rinse composition of the present invention. These compounds may be slightly water-soluble or completely water-soluble and are characterized by the ability to release fluoride ions or fluoride-containing ions into water. Typical compounds that supply fluoride are inorganic fluoride salts such as soluble alkali metal, alkaline earth metal and heavy metal salts such as sodium fluoride, potassium fluoride, ammonium fluoride, cupric fluoride, Zinc fluoride, stannic fluoride, tin fluoride, barium fluoride, sodium hexafluorosilicate, ammonium hexafluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate, and fluorinated Sodium calcium pyrophosphate. Amine fluorides such as N′-octadecyltrimethylenediamine-N, N, N′-tris (2-ethanol) -hydrofluoride and 9-octadecenylamine hydrofluoride have also been used. Also good.

  In some embodiments, the compound providing the fluoride may be up to 0.15% (or about 0.15%) by weight of the composition, optionally from 0.001% (or about 0.001%). 0.1 wt% (or about 0.1 wt%), optionally 0.001 wt% (or about 0.001 wt%) to 0.05 wt% (or about 0.05 wt%) fluoride. Usually present in an amount sufficient to release.

Zinc salt In some embodiments, a zinc salt such as zinc chloride, zinc acetate or zinc citrate is used as a disinfectant sensation astringent, as a respiratory protection enhancer or as an anticalculus agent. An amount of% w / v (or about 0.0025% w / v) to 0.1% w / v (or about 0.1% w / v) may be added.

Irritation-sensitive mitigating agent In certain embodiments, the irritation-sensitive mitigating agent, i.e., the potassium salt of nitric acid and oxalic acid, is from 0.1% (or about 0.1%) to 5.0% (or about 5.0%) w / v may be incorporated into the present invention. Other potassium releasing compounds are also possible (eg KCl). High concentrations of calcium phosphate may also add some relief to irritation sensitivity. These substances are believed to act by either forming occlusive mineral surface deposits on the tooth surface or supplying potassium to the nerves in the tooth to depolarize the nerves. . A more detailed discussion of suitable stimulus-sensitive relaxation can be found in US Patent No. 20060137778 to Hodsh and US Patent No. 6,416,745 to Markowitz et al., Both of which are hereby incorporated by reference in their entirety. Incorporated into.

Anticalculus Agents In certain embodiments, compounds that have anticalculus effects (eg, polyphosphates, phosphonates, various carboxylates, polyaspartic acid, inositol phosphates, etc.) may be incorporated into the present invention. Also useful as an anticalculus agent is an anionic polymer polycarboxylate. Such materials are well known in the art and are used in the form of their free acids or partially or preferably fully neutralized water-soluble alkali metal salts (eg potassium and preferably sodium) or ammonium salts. . Preference is given to maleic anhydride or maleic acid and other polymerizable ethylenically unsaturated monomers, preferably methyl vinyl ether (methoxy) having a molecular weight (M.W.) of about 30,000 to about 1,000,000. Ethylene) and a copolymer of 1: 4 to 4: 1 by weight. These copolymers are, for example, GAF Chemicals Corporation's Gantrez AN 139 (MW 500,000), AN 119 (MW 250,000) and preferably S-97 Pharmaceutical Grade (MW 70,000). ).

Additional Ingredients The liquid or mouthwash of the present invention can be formulated to be substantially clear and / or colorless to the naked eye, but acceptable approval to impart an attractive color to the composition of the present invention. Preferably used food dyes are used. These can be selected from, but are not limited to, a long list of acceptable food dyes. Suitable dyes for this purpose include FD & C Yellow No. 5, FD & C Yellow No. 10, FD & C Blue No. 1, and FD & C Green No. 3. These are conventional amounts, usually 0.00001% w / v (or about 0.00001% w / v) to 0.0008% w / v (or about 0.0008% w / v) of the composition, optional Are added in individual amounts from 0.00035% w / v (or about 0.00035% w / v) to 0.0005% w / v (or about 0.0005% w / v).

  Other conventional ingredients, including ingredients known and used in the art, may be used in the liquid or mouthwash compositions of the present invention. Examples of these components include thickeners, suspending agents and softeners. Thickeners and suspending agents useful in the compositions of the invention are found in US Pat. No. 5,328,682 to Pullen et al., Which is hereby incorporated by reference in its entirety. In some embodiments, these are 0.1% w / v (about 0.1% w / v) to 0.6% w / v (or about 0.6% w / v) of the composition, optionally Incorporated in an amount of 0.5% w / v (or about 0.5% w / v).

  A more detailed description of useful oral care actives and / or inactive ingredients, as well as additional examples thereof, may be found in U.S. Patent No. 6,682,722 to Majeti et al. And No. 6,121,315 to Nair et al. Each of which is incorporated herein by reference in its entirety.

  In certain embodiments, the compositions of the present invention are free or substantially free of compounds that affect bioavailability. As used herein, a “compound that affects bioavailability” refers to any essential oil incorporated, such as by inactivating the essential oil by binding to the essential oil or otherwise. Means a compound that acts negatively on the bioavailability of When used in connection with a compound that affects bioavailability, “substantially free” means 5% (or about 5%) of the total composition weight (w / v), optionally Biological usage in an amount of less than 3% (or about 3%), optionally 1% (or about 1%), or optionally 0.1, or optionally less than 0.01% (or about 0.01%) It is defined as a formulation having a compound that acts on the function. In some embodiments, the compounds that affect bioavailability include polyethylene oxide / polypropylene oxide block copolymers such as poloxamers, polysorbates such as cyclodextrins, Tweens, and mixtures thereof. It is not limited to.

Method of Carrying Out the Invention The invention described herein in an illustrative manner can be practiced without any components, components, or steps not specifically disclosed herein.

  In certain embodiments, the composition of the present invention is applied to the soft surface of the teeth and / or oral cavity at least twice in succession, optionally at least 3 (or about 3) times (or more), or optionally Applied continuously at least 5 (or about 5) times (or more).

  When applied to the soft surface of the tooth and / or mouth, in certain embodiments, the composition is applied to the soft surface of the tooth and / or mouth for at least 10 (or about 10) seconds (or more), optionally 20 (or about 20) seconds, optionally 30 (or about 30) seconds, optionally 50 (or about 50) seconds, or optionally 60 (or about 60) seconds.

  Various embodiments of the invention have been described above. Each embodiment is provided by way of explanation of the invention, not limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the scope or spirit of the invention. By way of example, features illustrated or described as part of one embodiment can be used in another embodiment to create still further embodiments. Accordingly, the present invention is intended to embrace such modifications and changes as fall within the scope of the appended claims and their equivalents.

  The following examples are for illustrative purposes only and should in no way be construed as limiting the invention. Those skilled in the art will appreciate that various modifications can be made within the spirit and scope of the appended claims.

Example 1: Different ways of making formulations and the effect of increasing surfactant levels Nine propylene glycol-based in different ways using different surfactants approved for use in oral care products A mouthwash formulation was prepared. The formulations were tested for turbidity and antibacterial activity. Turbidity was assessed using a Laboratory Turbidimeter Model 2100N from Hach Company (Loveland, CO). In addition, the formulation is in vitro single species S. cerevisiae. Tested using a mutans biofilm model. 22 hours Mutans biofilm was grown (N = 96) and exposed to the formulation for 30 seconds with positive and negative controls. Sterile water was used as a negative control. After treatment, the biofilm was neutralized and rinsed. Biofilms were harvested by sonication using a Misonix XL-2000 Ultrasonic processor (Qsonica, LLC, Newtown, CT). The Celsis Rapid Detection RapidScreen kit (Celsis International PLC, Chicago) was used to lyse the bacteria with Celsis Luminex and the ATP from the bacteria was measured with the bioluminescence marker, Celsis LuminATE. A decrease in log RLU (relative luminescence) indicates that fewer bacteria are alive after treatment. Nine formulations are shown in Table 1. The final formulation was adjusted to pH 4.2 using 0.1 M NaOH or 0.1 M HCl when necessary.

  The method of mixing the formulation was as follows.

  Formulation 1A: Water was placed in an appropriately sized tank (or container) and then all remaining ingredients were added to the water and mixed until dispersed. Individual premixes were not made.

  Formulation 1B: In step 1, a polyol solvent (ie, propylene glycol) was placed in an appropriately sized tank (or container). The active oil and flavor were added to the polyol solvent in the tank and mixed until homogeneous and uniform to make a premix. In step 2, instead of adding sugar alcohol as the final component in the final step of the formulation process, add the surfactant, water, organic acid buffer, preservative, sweetener and dye to the premix before adding it, Mix until the formulation is homogeneous and uniform. In step 3, surfactant was added to the premix and mixed until the formulation was homogeneous and uniform. In step 4, water was added to the premix and mixed until the formulation was homogeneous and uniform. In step 5, organic acid buffer, preservative and sweetener were added to the premix and mixed until homogeneous and uniform. In step 6, the dye was added to the premix and mixed until the formulation was homogeneous and uniform.

  Formulations 1C, 1D, and 1E: In Step 1, a polyol solvent (ie, propylene glycol) was placed in an appropriately sized tank (or container). Organic acid buffer was added to the polyol solvent to form a first premix and mixed until homogeneous and uniform. In Step 2, instead of forming a second premix of the active oil and the second polyol solvent and adding the second premix to the third premix containing water, surfactant, preservative and sweetener, the active oil And flavor were added directly to the first premix and mixed until homogeneous and uniform. In step 3, a sugar alcohol co-solvent was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 4, a surfactant was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 5, water, sweetener and preservative were added to the first premix and mixed until homogeneous and uniform. In step 6, the dye was added to the first premix and mixed until the formulation was homogeneous and uniform. In formulations 1D and 1E, higher levels of surfactant were added compared to formulation 1C.

  Formulation 1F: In Step 1, in a suitably sized first tank (or container), 5% of the first polyol solvent (ie, propylene glycol) is added to the active oil and flavoring to ensure that they are homogeneous and uniform. Until mixed to form a first premix. In step 2, in a suitably sized second tank (or container), 2.0% of the second polyol solvent, which is the same as the first polyol solvent, is added to the organic acid buffer and homogeneous in the second tank. And mixed until uniform to form a second premix. In Step 3, instead of adding the surfactant, water, preservatives, sweetener and dye, the sugar alcohol solvent is added directly to the first premix instead of being added as the final component in the final step of the formulation process, and homogeneous and Mix until uniform. In step 4, a surfactant was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 5, water was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 6, the second premix was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 7, preservatives and sweeteners were added and mixed until homogeneous and uniform. In step 8, the dye was added and mixed until the formulation was homogeneous and uniform.

  Formulation 1G (using the process of the invention): In Step 1, 5.0% first polyol solvent (ie propylene glycol), active oil and flavor in a suitably sized first tank (or container). The ingredients were added and mixed until homogeneous and uniform to form a premix. In step 2, in a second tank (or container) of an appropriate size, 2.0% of the same second polyol solvent as the first polyol solvent is added to the organic acid buffer to make it homogeneous and uniform. Until a second premix was formed. In Step 3, a surfactant, preservative and sweetener were added to water in a suitably sized third tank (or container) and mixed until homogeneous and uniform to make a third premix. In step 4, the first premix was added to the third premix and mixed until homogeneous and uniform. In step 5, the second premix was added to the mixture of the first premix and the third premix and mixed until homogeneous and uniform. In step 6, the dye was added to the mixture of the three premixes and mixed until homogeneous and uniform. In step 7, sugar alcohol was added as a final component to the mixture of three premixes and mixed until the final mixture was homogeneous and uniform.

  Formulation 1H: In Step 1, form separate premixes (one premix containing active oil and another premix containing organic acid buffer) in an appropriately sized first tank (or container). Instead, both the organic acid buffer and the active oil were added to the polyol solvent (ie, propylene glycol) and flavor and mixed until homogeneous and uniform to form the first premix. In Step 2, instead of adding a sugar alcohol solvent as the last component of the final step of the formulation process in a suitably sized second tank (or container), the surfactant, preservative, sweetener and water are added. In addition, mixing until homogeneous and uniform formed a second premix. In step 3, the first premix was added to the second premix and mixed until homogeneous and uniform. In step 4, the dye was added to the mixture of the two premixes and mixed until homogeneous and uniform.

  Formulation 1I: In Step 1, in a first tank (or container) of appropriate size, 5.0% of the first polyol solvent (ie, propylene glycol) is added to the active oil and flavoring agent to make it homogeneous and uniform. To form a first premix. In step 2, in a suitably sized second tank (or container), add 2.0% of the second polyol solvent, the same as the first polyol solvent, to the organic acid buffer until homogeneous and uniform. Mixed to form a second premix. In step 3, in a suitably sized third tank (or container), add the surfactant, sorbitol, preservative and sweetener to the water and mix until homogeneous and uniform to add the third premix. Formed. In step 4, instead of adding the first premix to the third premix, the second premix was added to the third premix and mixed until homogeneous and uniform. In step 5, the first premix was added to the mixture of the second premix and the third premix and mixed until homogeneous and uniform. In step 6, the dye was added and mixed until uniform.

  In addition to listing the formulation ingredients, Table 1 shows the turbidimetric turbidity unit (NTU) turbidity test and the S.D. of log RLU and M-factor units. The result of a mutans biofilm kill test is shown. A typical M-factor for a commercially available alcohol-containing essential oil mouth rinse is about 1.87 (log RLU 5.8) in this model.

  Table 1 also shows that all formulations containing sodium lauryl sulfate (Formulations 1A, 1B, 1C and 1F-1I) show high bactericidal action (M-factor of 1.66 to 2.22). However, the turbidity of all three sodium lauryl sulfate formulations (1A, 1B and 1C) was high (NTU greater than about 10.5). Increasing the total surfactant concentration level to 2.0% (formulations 1D and 1E) improved the turbidity, but at such high surfactant concentration levels, the bactericidal action assessed by the M-factor is considerable. Decreased (M-factor = 0.03 and -0.01, respectively). Only the formulation formed by the inventive process of the present invention (Formulation 1G) gave both good efficacy (M-factor = 2.05) and lowest turbidity (NTU less than 4.0).

Embodiment
(1) a. ) Preparing a first premix composition comprising:
i. A first oil or oily component;
ii. Optionally, a first polyol solvent;
iii. Preparing a first premix composition optionally comprising a flavoring;
b. ) Preparing a second premix composition comprising:
i. A second oil or oily component having a degree of hydrophobicity less than the hydrophobicity of the first oil or oily component; and ii. Preparing a second premix composition comprising a second polyol solvent;
c. ) Preparing a third premix composition comprising:
i. At least one surfactant, and ii. Preparing a third premix composition comprising an aqueous phase comprising water;
d. ) Adding the first premix to the third premix;
e. ) Step d. Mixing said composition until uniform and homogeneous;
f. ) The second premix is step e. And mixing until uniform and homogeneous;
A method for preparing a liquid composition comprising:
(2) The method of embodiment 1, wherein the liquid composition is essentially free of alcohol.
(3) a sugar alcohol solvent is used in step f. 2) and mixed until the composition is uniform and homogeneous.
(4) The method according to embodiment 1, wherein the first oil or oily component is an antibacterial essential oil selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, and mixtures thereof.
(5) The method according to embodiment 4, wherein the antibacterial essential oil is a mixture of menthol, eucalyptol, methyl salicylate and thymol.
(6) The group in which the second oil or oily constituent is ascorbic acid, sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid, benzoic acid, salicylic acid, phthalic acid, phenolsulfonic acid, succinic acid, and mixtures thereof Embodiment 2. The method of embodiment 1, wherein the method is an organic acid selected from.
(7) The method according to embodiment 6, wherein the second oil or oily component is an organic acid selected from the group consisting of benzoic acid.
(8) The method of embodiment 1, wherein the first and second polyol solvents are selected from the group consisting of polyhydric alkanes, polyhydric alkane esters, polyalkene glycols and mixtures thereof.
(9) The method of embodiment 8, wherein the first and second polyol solvents are polyhydric alkanes.
(10) The method according to embodiment 9, wherein the polyhydric alkane is propylene glycol.

(11) The group wherein the sugar alcohol solvent is xylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol, dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol, erythritol and a mixture thereof. Embodiment 4. The method of embodiment 3 selected from.
(12) A method according to embodiment 11, wherein the sugar alcohol solvent is sorbitol.
(13) Step g. The composition of embodiment 1 has a turbidity of less than about 12 nephelometric turbidity units.
(14) Step g. 14. The method of embodiment 13, wherein the composition has a turbidity of less than about 10 nephelometric turbidity units.
(15) Step g. 15. The method of embodiment 14, wherein said composition has a turbidity of less than about 8 nephelometric turbidity units.
(16) A liquid composition produced by the process according to Embodiment 1.

Claims (16)

a. ) Preparing a first premix composition comprising:
i. A first oil or oily component;
ii. Optionally, a first polyol solvent;
iii. Preparing a first premix composition optionally comprising a flavoring;
b. ) Preparing a second premix composition comprising:
i. A second oil or oily component having a degree of hydrophobicity less than the hydrophobicity of the first oil or oily component; and ii. Preparing a second premix composition comprising a second polyol solvent;
c. ) Preparing a third premix composition comprising:
i. At least one surfactant, and ii. Preparing a third premix composition comprising an aqueous phase comprising water;
d. ) Adding the first premix to the third premix;
e. ) Step d. Mixing said composition until uniform and homogeneous;
f. ) The second premix is step e. And mixing until uniform and homogeneous;
A method for preparing a liquid composition comprising:   The method of claim 1, wherein the liquid composition is essentially free of alcohol.   A sugar alcohol solvent is used in step f. 2) and mixed until the composition is uniform and homogeneous.   The method of claim 1, wherein the first oil or oily component is an antimicrobial essential oil selected from the group consisting of menthol, eucalyptol, methyl salicylate, thymol, and mixtures thereof.   The method according to claim 4, wherein the antibacterial essential oil is a mixture of menthol, eucalyptol, methyl salicylate and thymol.   The second oil or oily component is selected from the group consisting of ascorbic acid, sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid, benzoic acid, salicylic acid, phthalic acid, phenolsulfonic acid, succinic acid and mixtures thereof. The method of claim 1, which is an organic acid.   The method of claim 6, wherein the second oil or oily component is an organic acid selected from the group consisting of benzoic acid.   The method of claim 1, wherein the first and second polyol solvents are selected from the group consisting of polyhydric alkanes, polyhydric alkane esters, polyalkene glycols, and mixtures thereof.   9. The method of claim 8, wherein the first and second polyol solvents are polyhydric alkanes.   The method of claim 9, wherein the polyhydric alkane is propylene glycol.   The sugar alcohol solvent is selected from the group consisting of xylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol, dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol, erythritol and mixtures thereof. The method according to claim 3.   The method of claim 11, wherein the sugar alcohol solvent is sorbitol.   Step g. The composition of claim 1 has a turbidity of less than about 12 turbidimetric turbidity units.   Step g. 14. The method of claim 13, wherein the composition has a turbidity of less than about 10 nephelometric turbidity units.   Step g. 15. The method of claim 14 wherein the composition has a turbidity of less than about 8 turbidimetric turbidity units.   A liquid composition made by the process of claim 1.